(a) Field of the Invention
The present invention relates to new substituted sulfonamides, their preparation and use as medicines and such as for the treatment of diseases where the involvement of thromboxane A.sub.2 is recognized.
(b) Description of Prior Art
Arachidonic acid which is exogeneous or released by phospholipids by the action of phospholipase A.sub.2 is converted into endoperoxides (prostaglandine G.sub.2 (PGG.sub.2) and into prostaglandine H.sub.2 (PGH.sub.2)) by means of cyclooxygenase. The thromboxane synthetase thereafter catalyzes the conversion of PGH.sub.2 into thromboxane A.sub.2 (TXA.sub.2). The latter is capable, at very low concentrations, to induce serious biological disorders, such as platelet aggregation, vasoconstriction, bronchoconstriction, participating in the loss of integrity of the vascular membrane, thus making it responsible for certain diseases of the circulatory system and the respiratory system. These pathophysiological actions pass through the intermediary of receptors which can collect thromboxane A.sub.2 as well as the endoperoxides PGG.sub.2 /PGH.sub.2.
A method of inhibiting the effects of thromboxane A.sub.2 is to use selective antagonists of the receptors TXA.sub.2 /PGH.sub.2 and many products acting according to this mechanism are described in the art: see for example U.S. Pat. Nos. 4,443,477 and 4,861,913.
U.S. Pat. No. 4,443,477 describes sulfonamidobenzenecarboxylic acids which inhibit platelet aggregation, lower seric lipids and which have a general structure: ##STR2## where R is an hydrogen atom or a lower alkyl radical, R.sub.1 is an alkyl or aryl or aralkyl or aralkenyl radical, where the aryl group may possibly be in each case substituted by one or more of the following groups: hydroxyl, halogen, trifluoromethyl, lower alkyl or alkoxy or acyl, carboxy or alkoxycarbonyl; n is 1, 2 or 3 and W is a bond or an aliphatic hydrocarbon chain which is linear or not linear, containing a double or saturated bond, as well as the physiologically acceptable salts, esters and physiologically acceptable amides.
U.S. Pat. No. 4,861,913 describes bicyclic derivatives of sulfonamides which are inhibitors of platelet aggregation induced by thromboxane A.sub.2, inhibitors of vasoconstriction and of bronchoconstriction and which have the following general structure: ##STR3## where R.sub.1 is a hydrogen atom or a lower alkyl group; R.sub.2 is an alkyl radical or an aryl residue which is possibly substituted or an aralkyl group or a heterocycle; R.sub.3 represents an hydrogen atom or a methyl group; X is an alkylene chain or an alkenylene chain which is possibly substituted by a fluorine atom and may contain oxygen or sulfur and/or a phenylene group in the chain; Y represents an alkylene or alkenylene chain or an atom of oxygen or sulfur; m is 0 or 1; n is 0, 1 or 2.